Electrochemical Hemoglobin Biosensors for Point-of-Care Diagnostics

Hemoglobin (Hb) and its glycated variant (HbA1c) are essential clinical biomarkers for diagnosing anemia, acute hemorrhage, and long-term glycemic control. The growing demand for decentralized point-of-care (POC) testing has accelerated the development of rapid, inexpensive, and portable electrochemical sensing platforms. These technologies exploit the intrinsic redox activity of the heme prosthetic group, yet achieving efficient direct electron transfer (DET) remains a fundamental challenge because the electroactive iron center is deeply embedded within the globin structure. This review critically examines recent advances in electrochemical Hb sensing, tracing the evolution of electrode architectures from conventional carbon substrates to nanostructured materials, including graphene, MXenes, metal–organic frameworks (MOFs), and molecularly imprinted polymers (MIPs). We compare the advantages and limitations of non-enzymatic biomimetic platforms and affinity-based sensing strategies, including aptamer- and antibody-based biosensors, with emphasis on electron-transfer efficiency, molecular selectivity, analytical performance, and suitability for POC implementation. Beyond analytical performance, we evaluate the principal barriers to clinical translation, including biofouling, whole-blood matrix effects, viscosity-dependent mass transport, manufacturing scalability, and the persistent gap between validation in synthetic media and performance in clinical samples. Finally, we discuss emerging applications in wearable menstrual health monitoring and ingestible gastrointestinal bleeding sensors, highlighting the integration of advanced electrochemical materials with miniaturized electronics as a pathway toward practical, consumer-oriented diagnostics.